Main Findings and Interpretation:
Our data demonstrate that pregnancies compromised by AFLP show
exceedingly higher sFlt-1 and higher PLGF serum levels compared to
pregnancies affected by HELLP syndrome. This biochemical phenomenon
should focus our attention to diagnose or to rule out AFLP in women
presenting with pregnancy-associated liver disorders. Moreover, this
altered angiogenic pattern also underscores that AFLP and HELLP syndrome
are two distinct entities. Similar to our findings, compared to
pregnancies comprised to HELLP syndrome, altered angiogenic profile
patterns were found in AFLP patients in a case reports as well as in
case series.16, 17 These reports together with our
findings are important novel insights, particularly since prospective
studies will barely succeed due to the extremely low incidence of
AFPL.5
Clinically it may be difficult to distinguish AFLP from other
pregnancy-related diseases such as preeclampsia and HELLP syndrome due
to the similarity of symptoms and laboratory features. However, a timely
suspicion of AFLP is crucial for offering prompt diagnostic work up,
delivery and intensive supporting care preventing deleterious maternal
and neonatal outcomes. To date, applying the Swansea criteria reflects
the best diagnostic strategy to identify AFLP. However, applying these
criteria may delay the diagnosis of AFLP since they seem to be most
efficient when the disease is already in an advanced state and
life-threatening complications are occurring.22 Our
data demonstrate that an s-Flt1 value >31100 pg/ml may be
an additional parameter, if not even a key criterion, besides the
Swansea criteria, to focus our attention on the differential diagnosis
of AFLP. We postulate that sFlt-1 levels may herald AFLP prior to the
presence of the Swansea criteria and before the patient is already
severely ill. This gain of time may allow a coordinated peripartal
management in a multidisciplinary setting.
Elevated sFlt-1 serum levels have been observed also in various
non-obstetrical clinical situations including liver
diseases.23 Our findings of very high sFlt-1 values in
AFLP patients may be explained by the enormous inflammatory stimulus
involving various organ systems leading to proteinuria and altered blood
pressure. This common pathomechanism involving sFlt-1 may explain why
AFLP share similar features with preeclampsia and in particular with
HELLP syndrome, which in turn delay the diagnosis or the differentiation
of these pregnancy complications.